دورية أكاديمية
Facioscapulohumeral dystrophy weakened sarcomeric contractility is mimicked in induced pluripotent stem cells‐derived innervated muscle fibres
| العنوان: | Facioscapulohumeral dystrophy weakened sarcomeric contractility is mimicked in induced pluripotent stem cells‐derived innervated muscle fibres |
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| المؤلفون: | Camille Laberthonnière, Elva‐Maria Novoa‐del‐Toro, Mégane Delourme, Raphaël Chevalier, Natacha Broucqsault, Kilian Mazaleyrat, Nathalie Streichenberger, Véronique Manel, Rafaëlle Bernard, Emmanuelle Salort Campana, Shahram Attarian, Karine Nguyen, Jérôme D. Robin, Anais Baudot, Frédérique Magdinier |
| المصدر: | Journal of Cachexia, Sarcopenia and Muscle, Vol 13, Iss 1, Pp 621-635 (2022) |
| بيانات النشر: | Wiley |
| سنة النشر: | 2022 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Facioscapulohumeral dystrophy, Induced pluripotent stem cells, System biology, Pathophysiology, Sarcomere, Muscle contraction, Diseases of the musculoskeletal system, RC925-935, Human anatomy, QM1-695 |
| الوصف: | Background Facioscapulohumeral dystrophy (FSHD) is a late‐onset autosomal dominant form of muscular dystrophy involving specific groups of muscles with variable weakness that precedes inflammatory response, fat infiltration, and muscle atrophy. As there is currently no cure for this disease, understanding and modelling the typical muscle weakness in FSHD remains a major milestone towards deciphering the disease pathogenesis as it will pave the way to therapeutic strategies aimed at correcting the functional muscular defect in patients. Methods To gain further insights into the specificity of the muscle alteration in this disease, we derived induced pluripotent stem cells from patients affected with Types 1 and 2 FSHD but also from patients affected with Bosma arhinia and microphthalmia. We differentiated these cells into contractile innervated muscle fibres and analysed their transcriptome by RNA Seq in comparison with cells derived from healthy donors. To uncover biological pathways altered in the disease, we applied MOGAMUN, a multi‐objective genetic algorithm that integrates multiplex complex networks of biological interactions (protein–protein interactions, co‐expression, and biological pathways) and RNA Seq expression data to identify active modules. Results We identified 132 differentially expressed genes that are specific to FSHD cells (false discovery rate < 0.05). In FSHD, the vast majority of active modules retrieved with MOGAMUN converges towards a decreased expression of genes encoding proteins involved in sarcomere organization (P value 2.63e−12), actin cytoskeleton (P value 9.4e−5), myofibril (P value 2.19e−12), actin–myosin sliding, and calcium handling (with P values ranging from 7.9e−35 to 7.9e−21). Combined with in vivo validations and functional investigations, our data emphasize a reduction in fibre contraction (P value < 0.0001) indicating that the muscle weakness that is typical of FSHD clinical spectrum might be associated with dysfunction of calcium release (P value < ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2190-6009 2190-5991 |
| العلاقة: | https://doi.org/10.1002/jcsm.12835Test; https://doaj.org/toc/2190-5991Test; https://doaj.org/toc/2190-6009Test; https://doaj.org/article/8f932ee1e4384c53a16531a5f4c02563Test |
| DOI: | 10.1002/jcsm.12835 |
| الإتاحة: | https://doi.org/10.1002/jcsm.12835Test https://doaj.org/article/8f932ee1e4384c53a16531a5f4c02563Test |
| رقم الانضمام: | edsbas.E2DEBD1B |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 21906009 21905991 |
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| DOI: | 10.1002/jcsm.12835 |